7-44220272-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001220.5(CAMK2B):c.1791G>A(p.Pro597Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,612,312 control chromosomes in the GnomAD database, including 138,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P597P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.36 ( 10740 hom., cov: 33)

Exomes 𝑓: 0.42 ( 128176 hom. )

Consequence

CAMK2B
NM_001220.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.83

Publications

36 publications found

Variant links:

Genes affected

CAMK2B (HGNC:1461): (calcium/calmodulin dependent protein kinase II beta) The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

CAMK2B Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 40
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
intellectual disability, autosomal dominant 54
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CAMK2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-44220272-C-T is Benign according to our data. Variant chr7-44220272-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2B	NM_001220.5 link	c.1791G>A	p.Pro597Pro	synonymous_variant	Exon 23 of 24	ENST00000395749.7	NP_001211.3	Q13554-1A4D2J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2B	ENST00000395749.7 link	c.1791G>A	p.Pro597Pro	synonymous_variant	Exon 23 of 24	1	NM_001220.5	ENSP00000379098.2		Q13554-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55317

AN:

151942

Hom.:

10736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.514

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.343

GnomAD2 exomes

AF:

0.406

AC:

100979

AN:

248552

AF XY:

0.411

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.415

AC:

606688

AN:

1460254

Hom.:

128176

Cov.:

AF XY:

0.416

AC XY:

301957

AN XY:

726418

show subpopulations

African (AFR)

AF:

0.207

AC:

6917

AN:

33468

American (AMR)

AF:

0.369

AC:

16498

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

11943

AN:

26122

East Asian (EAS)

AF:

0.333

AC:

13202

AN:

39696

South Asian (SAS)

AF:

0.430

AC:

37097

AN:

86230

European-Finnish (FIN)

AF:

0.508

AC:

26656

AN:

52506

Middle Eastern (MID)

AF:

0.354

AC:

2041

AN:

5766

European-Non Finnish (NFE)

AF:

0.421

AC:

467864

AN:

1111416

Other (OTH)

AF:

0.405

AC:

24470

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17977

35954

53931

71908

89885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14378

28756

43134

57512

71890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.364

AC:

55332

AN:

152058

Hom.:

10740

Cov.:

AF XY:

0.371

AC XY:

27563

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.219

AC:

9074

AN:

41468

American (AMR)

AF:

0.358

AC:

5484

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3468

East Asian (EAS)

AF:

0.375

AC:

1935

AN:

5160

South Asian (SAS)

AF:

0.431

AC:

2077

AN:

4818

European-Finnish (FIN)

AF:

0.514

AC:

5445

AN:

10584

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28712

AN:

67946

Other (OTH)

AF:

0.349

AC:

735

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1771

3543

5314

7086

8857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.389

Hom.:

23538

Bravo

AF:

0.347

EpiCase

AF:

0.400

EpiControl

AF:

0.404

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CAMK2B-related disorder

Benign:1

Jul 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability, autosomal dominant 54

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

-3.8

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over